Objective Scleroderma (SSc) is a chronic inflammatory autoimmune disease characterized by fibrosis in the skin and internal organs. In SSc, the heart, lung, kidney, gastrointestinal (GIS) system, muscle, and peri-articular structures are damaged. There is no study of the relationship between SSc type, stage, pathogenesis, organ involvement, and Wnt signaling. In this study, we aimed to show the relationship of the Wnt gene family and antagonists in SSc subtypes and different organ involvement. Methods Eighty-five SSc patients and 77 controls were included in this study. The gene expressions and protein levels of the Wnt family and antagonists were analyzed from blood samples. The relationship between these parameters and disease stage, type, and organ involvement were evaluated. Results Wnt-1, Wnt-10b, Wnt-2, and Wnt-6 gene expressions are increased and Axin-2, DKK-1, and Kremen protein expressions are decreased in SSc. Wnt-3a and Wnt-10a gene expressions are increased in generalized SSc compared to limited SSc. Wnt-1, Wnt-2 gene expressions are increased significantly in pulmonary arterial hypertension (PAH)(+) SSc compared to PAH(-) SSc. There was a positive correlation between the modified Rodnan skin score and Wnt-2 in SSc. There was a significant positive correlation between GIS involvement score and Wnt-1, Wnt-2, Wnt-4, Wnt-8a, Wnt-9b in SSc. Conclusion Wnt-1 and Wnt-2 were found higher in scleroderma and organ involvement. They may play a role in the pathogenesis of the disease.